Risk of newly detected infections and cervical abnormalities in women seropositive for naturally acquired human papillomavirus type 16/18 antibodies: analysis of the control arm of PATRICIA

Xavier Castellsagué, Paulo Naud, Song-Nan Chow, Cosette M Wheeler, Maria Julieta V Germar, Matti Lehtinen, Jorma Paavonen, Unnop Jaisamrarn, Suzanne M Garland, Jorge Salmerón, Dan Apter, Henry Kitchener, Julio C Teixeira, S Rachel Skinner, Genara Limson, Anne Szarewski, Barbara Romanowski, Fred Y Aoki, Tino F Schwarz, Willy A J Poppe, F Xavier Bosch, Newton S de Carvalho, Klaus Peters, Wiebren A A Tjalma, Mahboobeh Safaeian, Alice Raillard, Dominique Descamps, Frank Struyf, Gary Dubin, Dominique Rosillon, Laurence Baril, Xavier Castellsagué, Paulo Naud, Song-Nan Chow, Cosette M Wheeler, Maria Julieta V Germar, Matti Lehtinen, Jorma Paavonen, Unnop Jaisamrarn, Suzanne M Garland, Jorge Salmerón, Dan Apter, Henry Kitchener, Julio C Teixeira, S Rachel Skinner, Genara Limson, Anne Szarewski, Barbara Romanowski, Fred Y Aoki, Tino F Schwarz, Willy A J Poppe, F Xavier Bosch, Newton S de Carvalho, Klaus Peters, Wiebren A A Tjalma, Mahboobeh Safaeian, Alice Raillard, Dominique Descamps, Frank Struyf, Gary Dubin, Dominique Rosillon, Laurence Baril

Abstract

Background: We examined risk of newly detected human papillomavirus (HPV) infection and cervical abnormalities in relation to HPV type 16/18 antibody levels at enrollment in PATRICIA (Papilloma Trial Against Cancer in Young Adults; NCT00122681).

Methods: Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative vs seropositive women (15-25 years) in the control arm (DNA negative at baseline for the corresponding HPV type [HPV-16: n = 8193; HPV-18: n = 8463]).

Results: High titers of naturally acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASCUS+), and cervical intraepithelial neoplasia grades 1/2 or greater (CIN1+, CIN2+). For HPV-18, although seropositivity was associated with lower risk of ASCUS+ and CIN1+, no association between naturally acquired antibodies and infection was demonstrated. Naturally acquired HPV-16 antibody levels of 371 (95% confidence interval [CI], 242-794), 204 (95% CI, 129-480), and 480 (95% CI, 250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASCUS+, respectively.

Conclusions: Naturally acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type.

Keywords: HPV; cervical abnormality; infection; naturally acquired antibodies; risk reduction.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Participant disposition. Abbreviations: ASCUS, atypical squamous cells of undetermined significance; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; MO, Month 0; TVC-E, total vaccinated cohort for efficacy.
Figure 2.
Figure 2.
Cumulative probability of detecting an incident or 6-month persistent infection or developing atypical squamous cells of undetermined significance or greater (ASCUS+) associated with human papillomavirus type 16 (HPV-16). A, Incident HPV-16 infection. B, HPV-16 six-month persistent infection. C, ASCUS+ associated with HPV-16.
Figure 2.
Figure 2.
Cumulative probability of detecting an incident or 6-month persistent infection or developing atypical squamous cells of undetermined significance or greater (ASCUS+) associated with human papillomavirus type 16 (HPV-16). A, Incident HPV-16 infection. B, HPV-16 six-month persistent infection. C, ASCUS+ associated with HPV-16.
Figure 3.
Figure 3.
Cumulative probability of detecting an incident or 6-month persistent infection or developing atypical squamous cells of undetermined significance or greater (ASCUS+) associated with human papillomavirus type 18 (HPV-18). A, Incident HPV-18 infection. B, HPV-18 six-month persistent infection. C, ASCUS+ associated with HPV-18.
Figure 3.
Figure 3.
Cumulative probability of detecting an incident or 6-month persistent infection or developing atypical squamous cells of undetermined significance or greater (ASCUS+) associated with human papillomavirus type 18 (HPV-18). A, Incident HPV-18 infection. B, HPV-18 six-month persistent infection. C, ASCUS+ associated with HPV-18.
Figure 4.
Figure 4.
Relationship between initial antibody level and 6-month persistent infection or atypical squamous cells of undetermined significance or greater (ASCUS+) associated with human papillomavirus type 16. A, 6-month persistent infection. B, ASCUS+. The dot size is proportional to the number of subjects, the gray dot represents all seronegative subjects, and red dots represent approximately 5-percentile classes of seropositive subjects. The solid blue line corresponds to the Poisson regression model (the dotted lines are 95% confidence limits). The dotted red lines correspond to a 50%, 70%, and 90% reduction of the incidence of the endpoint (6-month persistent infection or ASCUS+), and the values in red are the corresponding threshold values of antibody titer. Sensitivity analyses including the covariates of age at first sexual intercourse and smoking history, or including only a subset of 100 seronegative subjects, produced similar results. For example, including the covariates of age at first sexual intercourse and smoking history for all seronegative subjects, the estimated antibody titers (with 95% confidence interval) yielding 90%, 70%, and 50% reductions in 6-month persistent infection were 180 (118–377), 94 (62–197), and 54 (36–114) EU/mL, respectively. Abbreviations: CI, confidence interval; ELISA, enzyme-linked immunosorbent assay; HPV-16, human papillomavirus type 16.

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Source: PubMed

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